Hydrocolloids that are available from higher plants have been known for years. Such hydrocolloids include, e.g., guar gum, locust bean gum (also referred to as carob gum), karaya gum, gum tragacanth and the like. These hydrocolloids, particularly guar gum, have found uses as food additives as thickeners, binders, stabilizers, moisture retainers, etc.; as dietary supplements for treating constipation; as pharmaceutical excipients to affect the binding, disintegrating or thickening characteristics of formulations of certain drugs; as flocculants, floatation agent, thickeners, binders, friction reducers, temporary plugging agents, etc., in the mining and oil well drilling industries.
Generally, these naturally occurring hydrocolloids are available in various levels of purity which may vary from source to source. The primary component of guar gum and locust bean gum is a galactomannan-based polysaccharide that consists of linear chains of (1.fwdarw.4) linked .beta.-D-mannopyranosyl residues to which are attached (1.fwdarw.6) linked .alpha.-D-galactopyranocyl groups as single unit side-chains. The ratio of galactopyranose residues (generally given as anhydrogalactose to mannopyroanose residues (generally given as anhydromannose) varies from about 1:9 (about 10% by weight anhydrogalactose) to about 1:1.0 (about 50% by weight anhydrogalactose) depending on the source of the galactomannan. (See, e.g., Anderson, E. "Endosperm mucilagers of legumes: Occurrence and Composition," Ind. Eng. Chm. (1949) 41:2887-90.) Unfortunately, associated with the galactomannan-based polysaccharide are various impurities which can have an unpredictable and adverse affect on the composition as it is used in the pharmaceutical industry.
To obtain commercial grade galactomannan (e.g. guar gum from the guar seed), the hull (which is about 14-17% of the seed) is loosened by water soaking, then removed by multistage grinding and sifting, which takes advantage of the difference in hardness of the seed components. The germ, which is about 43-47% of the seed, is then removed by differential grinding using special types of hammer or roller mills. Finally, the remaining endosperm, which is about 35-45% of the seed and contains the galactomannan material, is ground to the desired particle size and marketed as food grade and pharmaceutical grade guar gum. Some of the remaining impurities include water (up to about 15% by weight), protein (up to about 10% by weight), acid insoluble matter (up to about 7% by weight), and ash (up to about 1.5%). Thus, up to 34% of the commercially available galactomannan-based polysaccharide compositions may be impurities.
It has been found that the commercially available guar gum generally does not provide a tablet with sufficient hardness ratings in higher concentrations to provide a tablet composition that will readily withstand the rigors of the tabletting process, storage and shipping. Thus, other excipients must be added to provide for the desired properties. Other excipients add additional bulk to the composition and make it more difficult to swallow as the tablet size increases.
It has been known that commercially available guar gum can be further purified by several methods. In one method, the gum is gently poured into water at about 60.degree. C. under strong stirring for 1-2 hours to form a 2 gram/liter solution, then is centrifuged in a batch centrifuge to remove insolubles. The galactomannan is then precipitated by adding 2 volumes of 95.degree. ethanol to 1 volume of the solution. The resulting precipitate is washed with ethanol, dried, crushed, dried under a vacuum and ground into a powder (see, 0. Noble, et al., Carbohydrate Polymers, 12 (1990) 203-217). The resulting material was then placed in water to determine the Theological properties of the resulting gels and whether this might have implications for the oil well drilling industry. Another method for purifying guar is disclosed which uses a jacalin-sepharose 4B absorbent in an affinity chromatography technique (see S. Chowdhury, Glycoconjuate J. (1988) 5:27-34). This resulted in 4-12 mg quantities of polysaccharide that was quite pure and could then be further chemically characterized. No use was suggested and no properties were tested.
Surprisingly, it has now been found that by using highly purified galactomannan (such as guar gum) as a pharmaceutical excipient at high levels a drug-containing tablet can be prepared that shows a significantly higher hardness rating than a comparable tablet using standard, commercially available guar gum. It has also been found that such tablet composition, as well as capsule compositions, exhibit a significantly greater degree of cohesion over a longer period of time as compared to a tablet composition using standard, commercially available guar gum. The highly purified galactomannan also exhibits a significantly faster hydration rate, as well as a higher viscosity.